188 research outputs found
«Ambulant akutteam - Et sikkerhetsbelte for mennesker i psykisk krise?»
The objective of this study is to contribute with in-depth knowledge based on personsâ subjective experiences within mental health crisis and support and help from a Crisis Resolution/Home Treatment (CR/HT) team. The study has a qualitative, exploratory design and qualitative interviews were conducted with seven persons. They have experiences with both inpatient treatment in hospitals and support from a CR/HT teams. The informants revealed a variety of experiences as service users in the different helping contexts. The experiences of the CR/HT teamâs accessibility, availability and flexibility, was highlighted as important. The Service users felt they were taken more seriously and met as a fellow human being in the home setting as opposed to hospital ward. The informants also emphasized how the CR/HT team helped them to feel more safe and secure. This study offers some in-depth insights of being on the receiving end of mental health services. It is important to include experience based user knowledge in the evidence base of practice development
Structure of the PPARα and -γ Ligand Binding Domain in Complex with AZ 242; Ligand Selectivity and Agonist Activation in the PPAR Family
AbstractBackground: The peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors belonging to the nuclear receptor family. The roles of PPARα in fatty acid oxidation and PPARγ in adipocyte differentiation and lipid storage have been characterized extensively. PPARs are activated by fatty acids and eicosanoids and are also targets for antidyslipidemic drugs, but the molecular interactions governing ligand selectivity for specific subtypes are unclear due to the lack of a PPARα ligand binding domain structure.Results: We have solved the crystal structure of the PPARα ligand binding domain (LBD) in complex with the combined PPARα and -γ agonist AZ 242, a novel dihydro cinnamate derivative that is structurally different from thiazolidinediones. In addition, we present the crystal structure of the PPARγ_LBD/AZ 242 complex and provide a rationale for ligand selectivity toward the PPARα and -γ subtypes. Heteronuclear NMR data on PPARα in both the apo form and in complex with AZ 242 shows an overall stabilization of the LBD upon agonist binding. A comparison of the novel PPARα/AZ 242 complex with the PPARγ/AZ 242 complex and previously solved PPARγ structures reveals a conserved hydrogen bonding network between agonists and the AF2 helix.Conclusions: The complex of PPARα and PPARγ with the dual specificity agonist AZ 242 highlights the conserved interactions required for receptor activation. Together with the NMR data, this suggests a general model for ligand activation in the PPAR family. A comparison of the ligand binding sites reveals a molecular explanation for subtype selectivity and provides a basis for rational drug design
«Lite visste vi hvordan vĂ„rsemesteret 2020 ville bli» â en tverrsnittstudie om pandemiens innvirkning pĂ„ intensivsykepleiestudentenes opplevelser i vĂ„rsemesteret 2020
Bakgrunn: Midt i vÄrsemesteret 2020 ble SARS-CoV-2 erklÊrt som pandemi. Studiehverdagen til landets intensivsykepleiestudenter ble brÄtt snudd pÄ hodet. All undervisning ble digital, og det var stor usikkerhet rundt gjennomfÞringen av praksisstudier. Mangelen pÄ intensivsykepleiere ble tydeliggjort, og utdanning av flere intensivsykepleiere mer kritisk.
Hensikt: Hensikten med studien var Ä kartlegge hvilke erfaringer intensivsykepleiestudentene i masterprogram hadde i vÄrsemesteret 2020 under covid-19-pandemien i Norge.
Metode: Studien er en beskrivende tverrsnittstudie med bruk av spĂžrreskjema. SpĂžrreskjemaet ble testet gjennom en pilotstudie, og sendt ut til alle landets intensivsykepleiestudenter som var i en videreutdanning som tilbĂžd mastergrad.
Resultat: Svarprosenten i studien var 29,2 prosent (n = 56). I teoretiske emner oppnÄdde 75 prosent av studentene sine lÊringsmÄl, og i kliniske emner oppnÄdde 76,8 prosent sine lÊringsmÄl. Digital undervisning medfÞrte at 60,7 prosent (n = 34) opplevde svekket studiemotivasjon. Halvparten av studentene opplevde redusert mulighet for veiledning i klinisk praksis, og 64,3 prosent erfarte at de ble brukt som arbeidskraft pÄ praksisstedet. Kun 34 prosent opplevde Ä fÄ beholde sin studentrolle, og 23,3 prosent tviler pÄ om de vil fortsette i yrket.
Konklusjon: VÄre resultater viser at fÞrste fase av pandemien medfÞrte endringer i undervisning, praksisstudier og veiledning, som medfÞrte lavere lÊringsutbytte og motivasjon. Flertallet av respondentene oppnÄdde likevel sine lÊringsmÄl i bÄde teoretiske og kliniske emner. Funnene viser at opplevelse av Ä bli brukt som arbeidskraft i praksis, og tap av studentrolle, er faktorer som reduserer motivasjon til Ä bÄde gjennomfÞre studiet og Ä fortsette i yrket. Studien viser at det Ä vÊre student i en pandemi er utfordrende fordi pandemien medfÞrte endringer i studenthverdagen.publishedVersio
Ligand binding mechanism in steroid receptors; from conserved plasticity to differential evolutionary constraints
Steroid receptor drugs have been available for more than half a century, but details 24 of the ligand binding mechanism has remained elusive. We solved X-ray structures of 25 the glucocorticoid and mineralocorticoid receptors to identify a conserved plasticity at 26 helix 6-7 region that extend the ligand binding pocket towards the receptor surface. 27 Since none of the endogenous ligands exploit this region, we hypothesized that it 28 constitutes an integral part of the binding event. Extensive all atom unbiased ligand 29 exit and entrance simulations corroborate a ligand binding pathway that gives the 30 observed structural plasticity a key functional role. Kinetic measurements reveal that 31 the receptor residence time correlate with structural rearrangements observed in both 32 structures and simulations. Ultimately, our findings reveal why nature has conserved 33 the capacity to open up this region and highlight how differences in the details of the 34 ligand entry process result in differential evolutionary constraints across the steroid 35 receptors.This study was supported by The European Research Council (2009-Adg25027-535 PELE) to V.G and by the SEV-2011-00067 grant of the Severo Ochoa Program. We 536 would like to acknowledge our AstraZeneca colleagues J. Hartleib, R.Unwin and 537 R.Knöll for helpful discussions. We also thank N. Blomberg (ELIXIR) and R. Neutze 538 (University of Gothenburg) for careful reading of the manuscript.Peer ReviewedPostprint (author's final draft
Up-regulation of cell cycle arrest protein BTG2 correlates with increased overall survival in breast cancer, as detected by immunohistochemistry using tissue microarray
<p>Abstract</p> <p>Background</p> <p>Previous studies have shown that the <it>ADIPOR1</it>, <it>ADORA1</it>, <it>BTG2 </it>and <it>CD46 </it>genes differ significantly between long-term survivors of breast cancer and deceased patients, both in levels of gene expression and DNA copy numbers. The aim of this study was to characterize the expression of the corresponding proteins in breast carcinoma and to determine their correlation with clinical outcome.</p> <p>Methods</p> <p>Protein expression was evaluated using immunohistochemistry in an independent breast cancer cohort of 144 samples represented on tissue microarrays. Fisher's exact test was used to analyze the differences in protein expression between dead and alive patients. We used Cox-regression multivariate analysis to assess whether the new markers predict the survival status of the patients better than the currently used markers.</p> <p>Results</p> <p>BTG2 expression was demonstrated in a significantly lower proportion of samples from dead patients compared to alive patients, both in overall expression (<it>P </it>= 0.026) and cell membrane specific expression (<it>P </it>= 0.013), whereas neither ADIPOR1, ADORA1 nor CD46 showed differential expression in the two survival groups. Furthermore, a multivariate analysis showed that a model containing BTG2 expression in combination with HER2 and Ki67 expression along with patient age performed better than a model containing the currently used prognostic markers (tumour size, nodal status, HER2 expression, hormone receptor status, histological grade, and patient age). Interestingly, BTG2 has previously been described as a tumour suppressor gene involved in cell cycle arrest and p53 signalling.</p> <p>Conclusions</p> <p>We conclude that high-level BTG2 protein expression correlates with prolonged survival in patients with breast carcinoma.</p
GLUT4 and UBC9 Protein Expression Is Reduced in Muscle from Type 2 Diabetic Patients with Severe Insulin Resistance
Subgroups of patients with type 2 diabetes mellitus demand large insulin doses to maintain euglycemia. These patients are characterized by severe skeletal muscle insulin resistance and the underlying pathology remains unclear. The purpose of this study was to examine protein expression of the principal glucose transporter, GLUT4, and associated proteins in skeletal muscle from type 2 diabetic patients characterized by severe insulin resistance.Seven type 2 diabetic patients with severe insulin resistance (mean insulin dose 195 IU/day) were compared with seven age matched type 2 diabetic patients who did not require insulin treatment, and with an age matched healthy control group. Protein expression of GLUT4 and associated proteins was assessed in muscle and fat biopsies using standard western blotting techniques.GLUT4 protein expression was significantly reduced by âŒ30 pct in skeletal muscle tissue from severely insulin resistant type 2 diabetic subjects, compared with both healthy controls and type 2 diabetic subjects that did not require insulin treatment. In fat tissue, GLUT4 protein expression was reduced in both diabetic groups. In skeletal muscle, the reduced GLUT4 expression in severe insulin resistance was associated with decreased ubiquitin-conjugating enzyme 9 (UBC9) expression while expression of GLUT1, TBC1D1 and AS160 was not significantly different among type 2 diabetic patients and matched controls.Type 2 diabetic patients with severe insulin resistance have reduced expression of GLUT4 in skeletal muscle compared to patients treated with oral antidiabetic drugs alone. GLUT4 protein levels may therefore play a role in the pathology behind type 2 diabetes mellitus among subgroups of patients, and this may explain the heterogeneous response to insulin treatment. This new finding contributes to the understanding of the underlying mechanisms for the development of extreme insulin resistance
Brukarens roll i vÀlfÀrdsforskning och utvecklingsarbete
Tekstene er fra forelesninger samt fra doktorantkurset "Brukarmedverkan i forskning och utvecklingsarbete inom hĂ€lso- och sjukvĂ„rd, socialt arbete och omsorg". Kurset ble avholdt vĂ„ren 2009.Fra omslag: PĂ„ 1980-talet blev âbrukareâ ett modeord i offentlig förvaltning och förvaltningsforskning.
Termen betecknar den som anvÀnder sig av vÀlfÀrdsservice (jfr. engelskans service user),
eller âslutmottagareâ av offentlig nyttighet eller Ă„tgĂ€rd.
Brukare av vÀlfÀrdstjÀnster vet hur hjÀlp och service fungerar i praktiken och kan dÀrför
ge synnerligen viktig Ă„terkoppling enligt devisen: âDen som har skorna pĂ„ fötterna vet
var de skaverâ. VĂ€lfĂ€rdsorganisationer har all anledning att involvera brukare i planering
och policyarbete i syfte att utveckla förmÄgan att göra rÀtt saker.
Det finns inte mycket dokumentation och forskning kring brukarmedverkan i utvecklingsarbete
och forskning pÄ vÀlfÀrdsomrÄdet. I synnerhet saknas kunskap om hur vÀlfÀrdstjÀnster
tas emot och realiseras i brukarens livssammanhang.
En ambition i doktorandkursen âbrukarmedverkan i forskning och utvecklingsarbete
inom hĂ€lso- och sjukvĂ„rd, socialt arbete och omsorgâ var att samla och presentera
kunskaper pÄ omrÄdet. Kursen genomfördes vÄren 2009 i ett unikt samarbete mellan
Karlstads Universitet, Sheffield University i England, Högskolan i Hedmark i Norge,
HÀlsohögskolan i Jönköping och Högskolan i BorÄs/FoU SjuhÀrad VÀlfÀrd.
Texterna i denna bok hÀrrör frÄn kursens förelÀsningar och paperarbeten. De ger
mÄnga exempel pÄ hur brukare kan involveras i forskning och utvecklingsarbete, och
presenterar en rad praktiska metoder för brukarsamverkan.
Boken rekommenderas till vÀlfÀrdens politiker och yrkespersoner, till studenter som
förbereder sig för vÀlfÀrdens yrken liksom till forskare och utvecklingsarbetare som vill utveckla
samarbete med brukare och brukarorganisationer. Den vÀnder sig givetvis Àven till
brukare och brukarorganisationer som vill engagera sig i forskning och utvecklingsarbete
Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients
Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEX(TM) Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89-1.28, p = 0.51) and 0.92 (95% CI 0.80-1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients.Peer reviewe
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